Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial

Yuri Ann Saito Loftus, G. Richard Locke, Ann E. Almazar, Ernest P. Bouras, Colin W. Howden, Brian E. Lacy, John K. DiBaise, Charlene M. Prather, Bincy P. Abraham, Hashem B. El-Serag, Paul Moayyedi, Linda M. Herrick, Lawrence Szarka, Michael Camilleri, Frank A. Hamilton, Cathy D. Schleck, Katherine E. Tilkes, Alan R. Zinsmeister, Nicholas J. Talley

Research output: Contribution to journalArticle

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Abstract

Objectives:The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.Methods:Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods.Results:GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy–Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43).Conclusions:GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.Am J Gastroenterol advance online publication, 14 March 2017; doi:10.1038/ajg.2017.52.

Original languageEnglish (US)
JournalAmerican Journal of Gastroenterology
DOIs
StateAccepted/In press - Mar 14 2017

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Dyspepsia
Antidepressive Agents
Genotype
Citalopram
Amitriptyline
Serotonin Uptake Inhibitors
Therapeutics
Serotonin Plasma Membrane Transport Proteins
Pharmacogenetics
Publications
Placebos
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Gastroenterology

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Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia : A Study from The Functional Dyspepsia Treatment Trial. / Saito Loftus, Yuri Ann; Locke, G. Richard; Almazar, Ann E.; Bouras, Ernest P.; Howden, Colin W.; Lacy, Brian E.; DiBaise, John K.; Prather, Charlene M.; Abraham, Bincy P.; El-Serag, Hashem B.; Moayyedi, Paul; Herrick, Linda M.; Szarka, Lawrence; Camilleri, Michael; Hamilton, Frank A.; Schleck, Cathy D.; Tilkes, Katherine E.; Zinsmeister, Alan R.; Talley, Nicholas J.

In: American Journal of Gastroenterology, 14.03.2017.

Research output: Contribution to journalArticle

Saito Loftus, YA, Locke, GR, Almazar, AE, Bouras, EP, Howden, CW, Lacy, BE, DiBaise, JK, Prather, CM, Abraham, BP, El-Serag, HB, Moayyedi, P, Herrick, LM, Szarka, L, Camilleri, M, Hamilton, FA, Schleck, CD, Tilkes, KE, Zinsmeister, AR & Talley, NJ 2017, 'Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial', American Journal of Gastroenterology. https://doi.org/10.1038/ajg.2017.52
Saito Loftus, Yuri Ann ; Locke, G. Richard ; Almazar, Ann E. ; Bouras, Ernest P. ; Howden, Colin W. ; Lacy, Brian E. ; DiBaise, John K. ; Prather, Charlene M. ; Abraham, Bincy P. ; El-Serag, Hashem B. ; Moayyedi, Paul ; Herrick, Linda M. ; Szarka, Lawrence ; Camilleri, Michael ; Hamilton, Frank A. ; Schleck, Cathy D. ; Tilkes, Katherine E. ; Zinsmeister, Alan R. ; Talley, Nicholas J. / Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia : A Study from The Functional Dyspepsia Treatment Trial. In: American Journal of Gastroenterology. 2017.
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abstract = "Objectives:The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.Methods:Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods.Results:GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88{\%}) and 246 (84{\%}) patients, respectively. Both polymorphisms were in Hardy–Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40{\%} vs. 31{\%} reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43).Conclusions:GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.Am J Gastroenterol advance online publication, 14 March 2017; doi:10.1038/ajg.2017.52.",
author = "{Saito Loftus}, {Yuri Ann} and Locke, {G. Richard} and Almazar, {Ann E.} and Bouras, {Ernest P.} and Howden, {Colin W.} and Lacy, {Brian E.} and DiBaise, {John K.} and Prather, {Charlene M.} and Abraham, {Bincy P.} and El-Serag, {Hashem B.} and Paul Moayyedi and Herrick, {Linda M.} and Lawrence Szarka and Michael Camilleri and Hamilton, {Frank A.} and Schleck, {Cathy D.} and Tilkes, {Katherine E.} and Zinsmeister, {Alan R.} and Talley, {Nicholas J.}",
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TY - JOUR

T1 - Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia

T2 - A Study from The Functional Dyspepsia Treatment Trial

AU - Saito Loftus, Yuri Ann

AU - Locke, G. Richard

AU - Almazar, Ann E.

AU - Bouras, Ernest P.

AU - Howden, Colin W.

AU - Lacy, Brian E.

AU - DiBaise, John K.

AU - Prather, Charlene M.

AU - Abraham, Bincy P.

AU - El-Serag, Hashem B.

AU - Moayyedi, Paul

AU - Herrick, Linda M.

AU - Szarka, Lawrence

AU - Camilleri, Michael

AU - Hamilton, Frank A.

AU - Schleck, Cathy D.

AU - Tilkes, Katherine E.

AU - Zinsmeister, Alan R.

AU - Talley, Nicholas J.

PY - 2017/3/14

Y1 - 2017/3/14

N2 - Objectives:The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.Methods:Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods.Results:GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy–Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43).Conclusions:GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.Am J Gastroenterol advance online publication, 14 March 2017; doi:10.1038/ajg.2017.52.

AB - Objectives:The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.Methods:Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods.Results:GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy–Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43).Conclusions:GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.Am J Gastroenterol advance online publication, 14 March 2017; doi:10.1038/ajg.2017.52.

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